A Double-Blind, Placebo-Controlled, First-in-Human Study of the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of ZE74-0282 in Healthy Volunteers.

Exclusion Criteria20

• History of anaphylaxis or other significant allergy which, in the opinion of the PI (or delegate), would interfere with the volunteer’s ability to participate in the study.
• History or presence of CS cardiovascular, pulmonary, hepatic, renal, haematological, gastrointestinal, endocrine, immunologic, dermatologic, psychiatric, or neurological disease/disorder, including any acute illness, within the past 3 months determined by the PI (or delegate) to be clinically relevant.
• History of surgery or hospitalisation within 3 months prior to screening, or surgery planned during the study.
• Any history of malignant disease in the last 10 years (excludes surgically resected skin squamous cell or basal cell carcinoma with histopathologically-confirmed clear margins).
• Presence of clinically relevant immunosuppression from, but not limited to, immunodeficiency conditions such as common variable hypogammaglobulinemia.
• History of risk factors for torsade de pointes (including a family history of long QT syndrome or sudden cardiac death) or a known arrythmia.
• Presence or having sequelae of gastrointestinal, liver (including Gilbert’s syndrome), kidney, or other conditions known to interfere with the absorption, distribution, metabolism, or excretion of drugs.
• Liver function test results elevated more than 1.5-fold above the ULN for gamma glutamyl transferase, bilirubin (total, conjugated and unconjugated), ALP, AST or ALT. Volunteers with ALP and/or ALT/AST above the limits specified may be included, at the discretion of the PI (or delegate), if the levels are unaccompanied by clinical signs and are determined to be normal variants.
• Estimated creatinine clearance less than 60 mL/min using the Cockcroft-Gault formula or serum creatinine greater than 1.5-fold above the ULN.
• A history of or positive test results for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg), or hepatitis C virus (HCV) antibodies at the screening visit.
• Positive drugs of abuse test (for a list of drugs tested refer to Section 11.1.8) or alcohol breath test results at the screening visit and/or on admission to the study site on Day -1. Note that positive carbon monoxide test at Screening is not exclusionary.
• Regular consumption of more than 10 standard alcoholic drinks/week and/or more than 4 standard alcoholic drinks on any one day, where 1 standard drink is 10 g of pure alcohol and is equivalent to 285 mL beer [4.9% Alc/Vol], 100 mL wine [12% Alc/Vol], or 30 mL spirit [40% Alc/Vol]).
• Participants must be nonsmokers for at least 3 months prior to the dose of study drug, have a negative carbon monoxide test at Screening and check-in (Day -1) to the clinical facility and refrain from smoking for the duration of the study. Note that positive carbon monoxide test at Screening is not exclusionary.
• Females who are breastfeeding or are planning to breastfeed from screening until 3 months after the dose of study drug.
• Unable to swallow oral medication.
• Current infection that requires systemically absorbed antibiotic, antifungal, antiparasitic or antiviral medication within 10 days prior to dose of study drug.
• Use of inactivated vaccines within 14 days or live vaccines within 30 days prior to the study drug administration and during the study.
• Participants must not take systemic immunosuppressive (e.g., corticosteroids, methotrexate, azathioprine, cyclosporine) or immunomodulating medications (e.g., interferon) within 28 days or 5 half-lives of any relevant agent(s) (whichever is longer) prior to dosing and during the study.
• Donation of blood or plasma within 30 days prior to dosing of study drug, or loss of whole blood of more than 500 mL within 30 days prior to first dose of study drug, or receipt of a blood transfusion within 1 year of the first dose of study drug.
• Participation in a clinical study of an investigational drug or investigational device within 30 days or 5 half-lives of the investigational drug (whichever is longer) prior to screening.